New Research
The MTA at 8 Years: Prospective Follow-up of Children Treated for Combined-Type ADHD in a Multisite Study

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Abstract

Objectives

To determine any long-term effects, 6 and 8 years after childhood enrollment, of the randomly assigned 14-month treatments in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA; N = 436); to test whether attention-deficit/hyperactivity disorder (ADHD) symptom trajectory through 3 years predicts outcome in subsequent years; and to examine functioning level of the MTA adolescents relative to their non-ADHD peers (local normative comparison group; N = 261).

Method

Mixed-effects regression models with planned contrasts at 6 and 8 years tested a wide range of symptom and impairment variables assessed by parent, teacher, and youth report.

Results

In nearly every analysis, the originally randomized treatment groups did not differ significantly on repeated measures or newly analyzed variables (e.g., grades earned in school, arrests, psychiatric hospitalizations, other clinically relevant outcomes). Medication use decreased by 62% after the 14-month controlled trial, but adjusting for this did not change the results. ADHD symptom trajectory in the first 3 years predicted 55% of the outcomes. The MTA participants fared worse than the local normative comparison group on 91% of the variables tested.

Conclusions

Type or intensity of 14 months of treatment for ADHD in childhood (at age 7.0–9.9 years) does not predict functioning 6 to 8 years later. Rather, early ADHD symptom trajectory regardless of treatment type is prognostic. This finding implies that children with behavioral and sociodemographic advantage, with the best response to any treatment, will have the best long-term prognosis. As a group, however, despite initial symptom improvement during treatment that is largely maintained after treatment, children with combined-type ADHD exhibit significant impairment in adolescence. Innovative treatment approaches targeting specific areas of adolescent impairment are needed.

Section snippets

Participants

The MTA participants were 579 children with DSM-IV ADHD combined type. Each of the six participating sites randomized 96 to 98 children to one of four treatment groups (MedMgt, Beh, Comb, and CC). At baseline (pretreatment), participants were 7.0 to 9.9 years of age (mean 8.5 years, SD 0.8 years). The MTA recruitment strategy, procedures for diagnosing ADHD, treatment specifics, and sample demographics have been described elsewhere.1, 2, 4, 5, 10, 11, 12, 13, 14

Participants were reassessed at

Medication Use Over Time

We first examined medication use because of its importance as a covariate in determining long-term treatment effects. As previously reported,6 medication use varied at 14, 24, and 36 months according to initial random assignment: mean (SD)—0.71 (0.24), 0.67 (0.35), 0.66 (0.41) for MedMgt; mean (SD)—0.71 (0.22), 0.69 (0.35), 0.67 (0.39) for Comb; mean (SD)—0.16 (0.28), 0.35 (0.44), 0.43 (0.46) for Beh; mean (SD)—0.54 (0.41), 0.58 (0.42), 0.59 (0.43) for CC, respectively. By the 6- and 8-year

Discussion

Three sets of findings resulted from this prospective longitudinal study of the MTA children into adolescence. Intent-to-treat analyses revealed no appreciable differences among the children based on their randomized treatment group assignment at 7 to 9 years of age. The ADHD symptom trajectory in childhood, however, was a strong predictor of outcome at both 6 and 8 years. Finally, despite overall maintenance of improvement in functioning relative to baseline (pretreatment), the MTA group as a

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    The NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA) was a National Institute of Mental Health (NIMH) cooperative agreement randomized clinical trial involving six clinical sites. Collaborators from the National Institute of Mental Health: Peter Jensen, M.D. (currently at Columbia University), L. Eugene Arnold, M.D., M.Ed. (currently at Ohio State University), Benedetto Vitiello, M.D. (Child and Adolescent Treatment and Preventive Interventions Research Branch), Kimberly Hoagwood, Ph.D. (currently at Columbia); previous contributors from NIMH to the early phase: John Richters, Ph.D. (currently at National Institute of Nursing Research); Donald Vereen, M.D. (currently at National Institute on Drug Abuse). Principal investigators and coinvestigators from the clinical sites are as follows: University of California, Berkeley/San Francisco: Stephen Hinshaw, Ph.D. (Berkeley), Glen Elliott, Ph.D., M.D. (San Francisco); Duke University: C. Keith Conners, Ph.D., Karen Wells, Ph.D., John March, M.D., M.P.H., Jeffery Epstein, Ph.D.; University of California, Irvine/Los Angeles: James Swanson, Ph.D. (Irvine), Dennis Cantwell, M.D., (deceased, Los Angeles), Timothy Wigal, Ph.D. (Irvine); Long Island Jewish Medical Center/Montreal Children's Hospital: Howard Abikoff, Ph.D. (currently at New York University School of Medicine), Lily Hechtman, M.D. (McGill University); New York State Psychiatric Institute/Columbia University/Mount Sinai Medical Center: Laurence Greenhill, M.D. (Columbia), Jeffrey Newcorn, M.D. (Mount Sinai School of Medicine); University of Pittsburgh: William Pelham, Ph.D. (currently at State University of New York at Buffalo), Betsy Hoza, Ph.D. (currently at University of Vermont), Brooke Molina, Ph.D., Patricia Houck, MS. Original statistical and trial design consultant: Helena Kraemer, Ph.D. (Stanford University). Follow-up phase statistical collaborators: Robert Gibbons, Ph.D. (University of Illinois at Chicago), Sue Marcus, Ph.D. (Mt. Sinai College of Medicine), Kwan Hur, Ph.D. (University of Illinois at Chicago). Collaborator from the Office of Special Education Programs/U.S. Department of Education: Thomas Hanley, Ed.D. Collaborator from Office of Juvenile Justice and Delinquency Prevention/Department of Justice: Karen Stern, Ph.D

    Disclosure: Dr. Jensen has received training and/or research funds from the Lowenstein Foundation, the Klingenstein Third Generation Foundation, the Annie E. Casey Foundation, Casey Family Programs, Novartis, Magellan, and Value Options. He participates in the speakers' bureaus of CMED, UCB Pharma, CME Outfitters, the Neuroscience Education Institute, Janssen-Ortho, and McNeil. He serves as a consultant to Best Practice, McNeil, Novartis, Janssen-Ortho, Otsuka, and Shire. Dr. Arnold has received research funding from the National Institute of Mental Health, Autism Speaks, Shire, Neuropharm, and CureMark. He has received consulting honoraria from Shire, Organon, Neuropharm, and Targacept. He has received speakers' honoraria from Shire. Dr. Swanson has received support for speaking at and travel to meetings from Janssen, UCB, and Novartis. Dr. Abikoff has received research funding from the National Institute of Mental Health and McNeil Pharmaceuticals. He has served on the ADHD advisory boards of Shire and Novartis. Dr. Greenhill is the recipient of the 2007 Elaine Schlosser Lewis Award for Greenhill L, Kollins S, Abikoff H, et al. Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD. J Am Acad Child Adolesc Psychiatry. 2006; 45:1284–1293. He has received research funding from Otsuka Pharmaceuticals, Bristol-Myers Squibb, the National Institute of Mental Health, and Johnson & Johnson, and has served as the chair for Pfizer's ziprasidone pediatric studies. Dr. Hechtman has received research funding from the National Institute of Mental Health, Eli Lilly, GlaxoSmithKline, Janssen-Ortho, Purdue Pharma, and Shire; has been on the speakers' bureaus of the National Institute of Mental Health, Eli Lilly, Janssen-Ortho, Purdue Pharma, and Shire; and has been on the advisory boards of Eli Lilly, Janssen-Ortho, Purdue Pharma, and Shire. Dr. Hoza has received research funding from MediaBalance. Dr. Newcorn has received grants for research support from Eli Lilly and Ortho-McNeil-Janssen. He has been a consultant and/or advisor to Abbott, BioBehavioral Diagnostics, Eli Lilly, Novartis, Ortho-McNeil-Janssen, Psychogenics, Sanofi-Aventis, and Shire, and a speaker for Ortho-McNeil-Janssen. Dr. Wigal has received research funding from Eli Lilly, Shire, McNeil, Otsuka, the National Institute of Mental Health, the National Institute on Drug Abuse, and the National Institute of Child Health and Human Development. He has consulted to and/or served on the speakers' bureaus of Otsuka, McNeil, and Shire. Dr. Wells receives workshop training fees from the REACH Institute and from the state of New York. The other authors report no conflicts of interest.

    The work reported was supported by cooperative agreement grants and contracts from the National Institute of Mental Health to the following: University of California, Berkeley: U01 MH50461, N01MH12009, and HHSN271200800005-C; Duke University: U01 MH50477, N01MH12012, and HHSN271200800009-C; University of California, Irvine: U01 MH50440, N01MH 12011, and HHSN271200800006-C; Research Foundation for Mental Hygiene (New York State Psychiatric Institute/Columbia University): U01 MH50467, N01 MH12007, and HHSN271200800007-C; Long Island-Jewish Medical Center U01 MH50453; New York University: N01MH12004 and HHSN271200800004-C; University of Pittsburgh: U01 MH50467, N01MH12010, and HHSN271200800008-C; and McGill University N01MH12008 and HHSN271200800003-C. The Office of Special Education Programs of the U.S. Department of Education, the Office of Juvenile Justice and Delinquency Prevention of the Justice Department, and the National Institute on Drug Abuse also participated in funding.

    The opinions and assertions contained in this report are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of Health and Human Services, the National Institutes of Health, or the National Institute of Mental Health.

    This article is the subject of an editorial by Dr. Philip L. Hazell in this issue.

    Clinical trial registration information—Multimodal Treatment Study of Children With Attention Deficit and Hyperactivity Disorder. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000388.

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